T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids.

Abstract : Glucocorticoids (GC) are steroid hormones that modulate T cell functions and restrain their hyperresponsiveness following stimulation. Naive T lymphocytes are sensitive to GC but become more resistant when they are activated. A balance between activation and inhibition signals is important for a targeted and effective T cell response. Thermal injury is characterized by an immune dysfunction and hyperactive T cells visible at day 10 postburn. In this study, our objective was to evaluate T cell sensitivity to GC following thermal injury and to identify mechanisms that could modulate their sensitivity. One mechanism that we hypothesized was increased p38 mitogen-activated protein kinase (MAPK) activity that could lead to GC resistance. Male C57BL/6 mice underwent a full-thickness 20% total body surface area. At 10 days postinjury, splenic T cells were isolated. Glucocorticoid receptor (GR) expression was higher in T cells from burn-injured mice. Interestingly, these cells were also less sensitive to GC-induced apoptosis prior to and poststimulation. Furthermore, anti-CD3-activated T cells from burn-injured mice showed increased proliferation and CD25 expression, which resisted corticosterone's (CORT) suppressive effect. Anti-CD3-activated CD4(+)CD44(+) memory cells from burn-injured mice expressed the highest level of CD25 and were resistant to CORT. Increased phosphorylation of p38 MAPK was also noted in activated T cells from burn-injured mice. Pharmacological inhibition of p38 MAPK decreased cell proliferation and normalized interferon-gamma (IFNgamma) production. In conclusion, we demonstrate that a unique event like burn injury induces a loss of sensitivity to GC in splenic T cells and have identified p38 MAPK as a key modulator for this resistance.
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Submitted on : Wednesday, May 1, 2013 - 11:10:32 PM
Last modification on : Friday, July 26, 2019 - 11:22:08 AM

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Michele d'Elia, Julie Patenaude, Charles Dupras, Jacques Bernier. T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids.. AJP - Endocrinology and Metabolism, American Physiological Society, 2010, 299 (2), pp.E299-307. ⟨10.1152/ajpendo.00084.2010⟩. ⟨pasteur-00819592⟩

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